Involvement of KATP channels in hydrogen sulfide‐induced increase in aqueous humor outflow (1060.3)

Involvement of K atp channels in hydrogen sulfide‐induced increase in aqueous humor outflow Jenaye Robinson 1 , Chinoso Ezeudu 1 , Leah Mitchell 1 , Madhura Chitnis 1 , Catherine Opere 2 , Sunny E. Ohia 1 ,Ya Fatou Njie‐Mbye 1 . 1 Department of Pharmaceutical Sciences, College of Pharmacy and Health sciences, Texas Southern University, Houston TX 77004, 2 Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University, Omaha, NE 68178 We have evidence that hydrogen sulfide (H 2 S), a novel gasotransmitter can increase aqueous humor (AH) outflow in porcine trabecular meshwork tissues (TM). Purpose : To investigate the underlying mechanism of H 2 S‐induced increase in AH outflow. Methods : Porcine ocular anterior segment explants were perfused with DMEM maintained at 37ºC, 5% CO 2 and constant pressure of 7.35 mmHg. Stabilized explants were exposed to the H 2 S‐releasing compound, sodium hydrosulfide (NaHS) and its substrate, L‐cysteine. Explants were also treated with the K ATP channel antagonist glibenclamide and H 2 S biosynthetic enzyme inhibitors, aminooxyacetic acid (AOA), or proparglyglycine (PAG). Results : L‐cysteine (1 nM ‐ 1μM) caused a dose‐dependent increase in outflow, reaching a maximal effect at 100 nM [153 ± 7.2% of basal (mean ± SE)]. The effect of L‐cysteine (100 nM) on AH outflow was completely attenuated by AOA (30 μM) and PAG (1 mM). Interestingly, NaHS (100 nM ‐ 10 µM) also produced a concentration‐dependent increase in AH outflow, reaching a maximal effect at 10 μM. Furthermore, the enhancement of outflow caused by NaHS (10 μM) was inhibited significantly ( p < 0.01) by glibenclamide (100 µM). Conclusions : We conclude that H 2 S‐induced increase AH outflow in porcine TM is dependent upon its intramural biosynthesis from L‐cysteine and, is mediated by K ATP channels. Grant Funding Source : Supported by NIH/NEI Grant R15EY022215